TFH-derived dopamine accelerates productive synapses in germinal centres

Ilenia Papa, David Saliba, Maurilio Ponzoni, Sonia Bustamante, Pablo F. Canete, Paula Gonzalez-Figueroa, Hayley A. McNamara, Salvatore Valvo, Michele Grimbaldeston, Rebecca A. Sweet, Harpreet Vohra, Ian A. Cockburn, Michael Meyer-Hermann, Michael L. Dustin, Claudio Doglioni and Carola G. Vinuesa ()
Additional contact information
Ilenia Papa: John Curtin School of Medical Research, Australian National University
David Saliba: Kennedy Institute of Rheumatology, Rheumatology and Musculoskeletal Sciences, University of Oxford
Maurilio Ponzoni: Ateneo Vita-Salute, IRCCS Scientific Institute San Raffaele
Sonia Bustamante: Bioanalytical Mass Spectrometry Facility, Mark Wainwright Analytical Centre, University of New South Wales
Pablo F. Canete: John Curtin School of Medical Research, Australian National University
Paula Gonzalez-Figueroa: John Curtin School of Medical Research, Australian National University
Hayley A. McNamara: John Curtin School of Medical Research, Australian National University
Salvatore Valvo: Kennedy Institute of Rheumatology, Rheumatology and Musculoskeletal Sciences, University of Oxford
Michele Grimbaldeston: Centre for Cancer Biology, University of South Australia and SA Pathology
Rebecca A. Sweet: John Curtin School of Medical Research, Australian National University
Harpreet Vohra: Imaging and Cytometry Facility, John Curtin School of Medical Research, Australian National University
Ian A. Cockburn: John Curtin School of Medical Research, Australian National University
Michael Meyer-Hermann: Helmholtz Centre for Infection Research
Michael L. Dustin: Kennedy Institute of Rheumatology, Rheumatology and Musculoskeletal Sciences, University of Oxford
Claudio Doglioni: Ateneo Vita-Salute, IRCCS Scientific Institute San Raffaele
Carola G. Vinuesa: John Curtin School of Medical Research, Australian National University

Nature, 2017, vol. 547, issue 7663, 318-323

Abstract: Abstract Protective high-affinity antibody responses depend on competitive selection of B cells carrying somatically mutated B-cell receptors by follicular helper T (TFH) cells in germinal centres. The rapid T–B-cell interactions that occur during this process are reminiscent of neural synaptic transmission pathways. Here we show that a proportion of human TFH cells contain dense-core granules marked by chromogranin B, which are normally found in neuronal presynaptic terminals storing catecholamines such as dopamine. TFH cells produce high amounts of dopamine and release it upon cognate interaction with B cells. Dopamine causes rapid translocation of intracellular ICOSL (inducible T-cell co-stimulator ligand, also known as ICOSLG) to the B-cell surface, which enhances accumulation of CD40L and chromogranin B granules at the human TFH cell synapse and increases the synapse area. Mathematical modelling suggests that faster dopamine-induced T–B-cell interactions increase total germinal centre output and accelerate it by days. Delivery of neurotransmitters across the T–B-cell synapse may be advantageous in the face of infection.

Date: 2017
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DOI: 10.1038/nature23013

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